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1.
J Endocrinol Invest ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965518

RESUMO

PURPOSE: The alpha7 nicotinic acetylcholine receptor (α7nAChR), involved in the modulation of inflammation and insulin sensitivity, is downregulated in white adipose tissue (WAT) of obese patients. This study aims to test the ability of a selective synthetic α7nAChR agonist, the spirocyclic Δ2-isoxazoline derivative (R)-(-)-ICH3 (ICH3), to counteract acute inflammation and obesity-associated modifications in WAT. METHODS: We employed the LPS-septic shock murine model, human primary adipocytes and diet-induced obese (DIO) mice. Inflammatory factor expression was assessed by ELISA and quantitative real-time PCR. Flow cytometry was employed to define WAT inflammatory infiltrate. Insulin signaling was monitored by quantification of AKT phosphorylation. RESULTS: In the septic shock model, ICH3 revealed antipyretic action and reduced the surge of circulating cytokines. In vitro, ICH3 stimulation (10 µM) preserved viability of human adipocytes, decreased IL-6 mRNA (P < 0.05) and blunted LPS-induced peak of TNFα (P < 0.05) and IL-6 (P < 0.01). Chronic administration of ICH3 to DIO mice was associated with lower numbers of CD8+ T cells (P < 0.05) and to changed WAT expression of inflammatory factors (Hp, P < 0.05; CD301/MGL1, P < 0.01; Arg-1, P < 0.05). As compared to untreated, ICH3 DIO mice exhibited improved insulin signaling in the skeletal muscle (P < 0.01) mirrored by an improved response to glucose load (ipGTT: P < 0.05 at 120 min). CONCLUSIONS: We proved that ICH3 is an anti-inflammatory drug, able to reduce inflammatory cytokines in human adipocytes and to blunt the effects of obesity on WAT inflammatory profile, on glucose tolerance and on tissue insulin sensitivity.

2.
Eur J Endocrinol ; 182(1): 11-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31652416

RESUMO

Objective: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). Results: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. Conclusions: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.

3.
Eur J Endocrinol ; 182(1): G1-G32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855556

RESUMO

Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.


Assuntos
Índice de Massa Corporal , Hipotireoidismo/diagnóstico , Obesidade/diagnóstico , Comorbidade , Endocrinologia , Humanos , Hipotireoidismo/epidemiologia , Obesidade/epidemiologia , Prevalência , Testes de Função Tireóidea
4.
J Endocrinol Invest ; 42(11): 1365-1386, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31111407

RESUMO

BACKGROUND: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. PURPOSE: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.

5.
J Endocrinol Invest ; 42(1): 61-73, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29704234

RESUMO

AIM: Lipodystrophy syndromes are rare heterogeneous disorders characterized by deficiency of adipose tissue, usually a decrease in leptin levels and, frequently, severe metabolic abnormalities including diabetes mellitus and dyslipidemia. PURPOSE: To describe the clinical presentation of known types of lipodystrophy, and suggest specific steps to recognize, diagnose and treat lipodystrophy in the clinical setting. METHODS: Based on literature and in our own experience, we propose a stepwise approach for diagnosis of the different subtypes of rare lipodystrophy syndromes, describing its more frequent co-morbidities and establishing the therapeutical approach. RESULTS: Lipodystrophy is classified as genetic or acquired and by the distribution of fat loss, which can be generalized or partial. Genes associated with many congenital forms of lipodystrophy have been identified that may assist in diagnosis. Because of its rarity and heterogeneity, lipodystrophy may frequently be unrecognized or misdiagnosed, which is concerning because it is progressive and its complications are potentially life threatening. A basic diagnostic algorithm is proposed. Effective management of lipodystrophy includes lifestyle changes and aggressive, evidence-based treatment of comorbidities. Leptin replacement therapy (metreleptin) has been found to improve metabolic parameters in many patients with lipodystrophy. Metreleptin is approved in the United States as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy and has been submitted for approval in Europe. CONCLUSIONS: Here, we describe the clinical presentation of known types of lipodystrophy, present an algorithm for differential diagnosis of lipodystrophy, and suggest specific steps to recognize and diagnose lipodystrophy in the clinical setting.


Assuntos
Tecido Adiposo/metabolismo , Lipodistrofia/diagnóstico , Lipodistrofia/terapia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Humanos , Resistência à Insulina/fisiologia , Leptina/administração & dosagem , Lipodistrofia/metabolismo , Resultado do Tratamento
6.
Sci Rep ; 8(1): 10318, 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29985450

RESUMO

Principal research on energy from thermonuclear fusion uses Deuterium-Tritium plasmas magnetically trapped in toroidal devices. As major scientific problem for an economic (i.e., really feasible) reactor, we must understand how to lead strongly heated plasmas to sustain a high fusion gain while large fraction of current is self-produced via the presence of strong pressure gradient. To suppress turbulent eddies that impair thermal insulation and pressure tight of the plasma, current drive (CD) is necessary. However, tools envisaged so far in ITER (International Thermonuclear Experiment Rector) are unable accomplishing this task that requires efficiently and flexibly matching the natural current profiles of plasma. Consequently, viability of a thermonuclear reactor should be problematic. Multi-megawatt radio-frequency (RF) power coupled to plasma would produce the necessary CD, but modelling results based on previous understanding found difficult the extrapolation of this CD concept to reactor conditions of high temperature plasma, and greater flexibility of method would also be required. Here we present new model results based on standard quasilinear (QL) theory that allow establish conditions to drive efficiently and flexibly the RF-driven current at large radii of the plasma column, as necessary for the goal of a reactor.

7.
Lipids Health Dis ; 17(1): 124, 2018 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-29793488

RESUMO

BACKGROUND: Hypercholesterolemia is a major risk factor for cardiovascular disorders and requires specific intervention through an adequate lifestyle (diet and physical exercise) and, if necessary, an appropriate drug treatment. Lipid-lowering drugs, although generally efficacious, may sometimes cause adverse events. A growing attention has been devoted to the correction of dyslipidemias through the use of dietary supplements. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid, named Argicolina (A), compared to a commercially available product containing monacolin K and coenzyme Q10, Normolip 5 (N). METHODS: This was a single center, controlled, randomized, open-label, cross-over clinical study enrolling 20 Caucasian outpatients aged 18-75 years with serum LDL-C between 130 and 180 mg/dL. Patients assumed two different dietary supplements (A and N) both containing monacolin K 10 mg for 8 weeks each, separated by a 4-week wash-out period. Evaluated parameters were: Total cholesterol (Tot-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose, aspartate aminotransferase, alanine aminotransferase, creatinekinase, gamma-glutamyl-transpeptidase, brachial arterial pressure and heart rate, measured at the start and at the end of each treatment period. Safety was monitored through the study. RESULTS: LDL-C decreased by 23.3% during treatment with N (p < 0.0001) and by 25.6% during treatment with A (p < 0.0001); the LDL-C mean reduction was 36.4 (95% CI: 45,6-27,1) mg/dL during N treatment and 40.1 (95% CI: 49.2-30,9) mg/dL during A treatment. Tot-C decreased significantly (p < 0.0001) within each treatment period. HDL-C increase was negligible during A whereas it was significant during N. TG diminished markedly during A and not significantly during N. The difference between treatments was not statistically significant for all variables. No serious or severe adverse events occurred during the study. CONCLUSIONS: Our results confirm the clinically meaningful LDL-C lowering properties of monacolin K. At variance with a supplement already in the market (N), the novel association (A) of monacolin K with L-arginine, coenzime Q10 and ascorbic acid also produces a significant reduction of triglycerides without significant effects on HDL. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03425630 .


Assuntos
Anticolesterolemiantes/administração & dosagem , LDL-Colesterol/sangue , Suplementos Nutricionais , Hipercolesterolemia/dietoterapia , Triglicerídeos/sangue , Adolescente , Adulto , Idoso , Análise de Variância , Arginina/administração & dosagem , Ácido Ascórbico/administração & dosagem , HDL-Colesterol/sangue , LDL-Colesterol/antagonistas & inibidores , Estudos Cross-Over , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Lovastatina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Triglicerídeos/antagonistas & inibidores , Ubiquinona/administração & dosagem , Ubiquinona/análogos & derivados
8.
J Endocrinol Invest ; 41(1): 83-89, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28741280

RESUMO

The pathogenesis of human obesity is the result of dysregulation of the reciprocal relationship between food intake and energy expenditure (EE), which influences daily energy balance and ultimately leads to weight gain. According to principles of energy homeostasis, a relatively lower EE in a setting of energy balance may lead to weight gain; however, results from different study groups are contradictory and indicate a complex interaction between EE and food intake which may differentially influence weight change in humans. Recently, studies evaluating the adaptive response of one component to perturbations of the other component of energy balance have revealed both the existence of differing metabolic phenotypes ("spendthrift" and "thrifty") resulting from overeating or underfeeding, as well as energy-sensing mechanisms linking EE to food intake, which might explain the propensity of an individual to weight gain. The purpose of this review is to debate the role that human EE plays on body weight regulation and to discuss the physiologic mechanisms linking EE and food intake. An increased understanding of the complex interplay between human metabolism and food consumption may provide insight into pathophysiologic mechanisms underlying weight gain, which may eventually lead to prevention and better treatment of human obesity.


Assuntos
Peso Corporal/fisiologia , Ingestão de Alimentos/fisiologia , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Obesidade/metabolismo , Composição Corporal/fisiologia , Humanos , Obesidade/etiologia , Fenótipo , Ganho de Peso/fisiologia
9.
Int J Obes (Lond) ; 41(11): 1676-1684, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28761130

RESUMO

BACKGROUND/OBJECTIVES: In lipodystrophy (LD) adipose tissue function to store lipids is impaired, leading to metabolic syndrome, similar to that found in obesity. Emerging evidence links dysmetabolism with disorders of the immune system. Our aim is to investigate whether T-cell populations with regulatory function and monocyte-derived macrophages (MDMs) are affected by LD and obesity. SUBJECTS/METHODS: Blood was collected from 16 LD, 16 obese (OB, BMI>30 kg m-2) and 16 healthy normal-weight women (CNT). Physical parameters, plasma lipid profile, glucose, HbA1c, leptin levels were determined. Flow cytometry was employed to assess the number of circulating CD4+/CD25hi regulatory T cells (Tregs) and invariant natural killer T (iNKT) cells. Characterization of MDMs included: 1. morphological/oil-Red-O staining analyses to define two morphotypes: lipid laden (LL) and spindle-like (sp) MDM; 2. gene expression studies; 3. use of conditioned medium from MDMs (MDMs CM) on human SGBS cells. RESULTS: As compared to CNT, LD and, to a lesser extent, obesity were associated with reduced Tregs and iNKTs (P<0.001 and P<0.01 for LD and OB, respectively), higher number of LL-MDMs (P<0.001 and P<0.01 for LD and OB, respectively), lower number of sp-MDMs (P<0.001 for both LD and OB), which correlated with increased paracrine stimulation of lipid accumulation in cells (P<0.001 and P<0.01 for LD and OB, respectively). LD MDMs showed decreased and increased expression for anti-inflammatory (IL10 and CD163) and pro-inflammatory (CD68 and CCL20) marker genes, respectively. Analysis of correlation indicated that Tregs are directly related with HDL (P<0.01) and inversely related with LL-MDM (P<0.001) and that LL-MDM are directly related with triglycerides (P<0.01) and oxidized LDL (P<0.01). CONCLUSIONS: LD and obesity are associated with changes in the immune system: a significant reduction in the number of T cells with regulatory function and a shift of MDM towards lipid accumulation. Lipid profile of the patients correlates with these changes.


Assuntos
Tecido Adiposo/metabolismo , Lipodistrofia/imunologia , Macrófagos/imunologia , Obesidade/imunologia , Linfócitos T/citologia , Adulto , Feminino , Citometria de Fluxo , Hemoglobina A Glicada , Humanos , Lipídeos/imunologia , Lipodistrofia/metabolismo , Lipodistrofia/patologia , Lipodistrofia/fisiopatologia , Contagem de Linfócitos , Ativação de Macrófagos , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia , Fenótipo , Linfócitos T/imunologia
11.
J Endocrinol Invest ; 40(2): 105-121, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27837466

RESUMO

BACKGROUND: Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are two fluorinated compounds widely used in industry because of their useful chemical characteristics. They were identified as endocrine disruptors due to their ability to interfere with thyroid function. The resistance of PFOA and PFOS to environmental degradation, their bio-accumulation in food chains, and their long half-life raised concern in the scientific community, and several studies were performed with the aim to establish the real dangerousness of these compounds for the human health. PURPOSE: The present review will focus on the effects of PFOA and PFOS on the thyroid gland taking into account in vitro experiments, animal studies, and human data. PFOS and PFOA reduce the circulating levels of thyroid hormones in diet-exposed animals, mainly by increasing their metabolic clearance rate. CONCLUSIONS: An accumulation of PFOS and PFOA was documented in thyroid cells, and a cytotoxic effect was observed after exposure to extremely high concentrations of these compounds. In environmentally exposed communities and in the general population, the most consistent effect of exposure to PFOA, and to a less extent to PFOS, is the occurrence of hypothyroidism. Women and children appear to be more at risk of developing mild thyroid failure. Pregnant women with circulating thyroid antibodies might be at risk of developing subclinical hypothyroidism, mainly when exposed at high doses of PFOS. The relative risks for thyroid cancer in people exposed to PFOA and PFOS were low and based on a few cases. Moreover, there was no consistent finding across all or even most studies.


Assuntos
Ácidos Alcanossulfônicos/metabolismo , Caprilatos/metabolismo , Fluorcarbonetos/metabolismo , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/metabolismo , Feminino , Humanos , Gravidez
12.
Clin Ter ; 166(3): e203-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26152633

RESUMO

The importance of the Type-1 helper (Th1) chemokines in RSV (respiratory syncytial virus) infection has been shown by several studies, in animal models, and in humans. The production of Th1 chemokines within the lower respiratory tract has been shown in patients with RSV bronchiolitis, particularly chemokine (C-X-C motif) ligand (CXCL)10/interferon-γ-inducible protein 10 (IP-10), whose plasma levels were markedly elevated in acute infection. RSV fusion (F) or large (G) protein treatment of fully differentiated primary normal human bronchial epithelial cells induces apical secretion of IP-10 and other chemokines. Exposure to environmental tobacco smoke is associated with an increase in the frequency and severity of respiratory infections, including bronchiolitis, and inhibited RSV-induced Interferon (IFN)-α in plasmacytoid dendritic cells as well as the release of IP-10. Vitamin D in airway epithelium decreases RSV induction of NF-kappaB-driven genes such as IFN-ß and IP-10. These findings highlight the role for the IP-10: chemokine (C-X-C motif) receptor (CXCR)3 signaling axis in RSV-infection by recruiting virus-specific T cells into the lung and promoting viral clearance.


Assuntos
Quimiocina CXCL10/biossíntese , Receptores CXCR3/biossíntese , Infecções por Vírus Respiratório Sincicial/fisiopatologia , Linfócitos T Auxiliares-Indutores/metabolismo , Animais , Humanos , Pulmão/fisiopatologia , Vírus Sincicial Respiratório Humano , Fatores de Risco , Poluição por Fumaça de Tabaco/efeitos adversos , Vitamina D/farmacologia
13.
Clin Obes ; 5(1): 22-30, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25611584

RESUMO

Eating dyscontrol constitutes a potential negative predictor for the outcome of treatment strategies for obese patients. The aim of this study was to examine the qualitative characteristics of eating dyscontrol in obese patients who engage in binge eating (BE) compared with those who do not (NBE), and to analyse the relationship between eating dyscontrol and axis-I, axis-II, spectrum psychopathology using instruments that explore mood, panic-agoraphobic, social-phobic, obsessive-compulsive and eating disorders spectrum psychopathology (SCI-MOODS-SR, SCI-PAS-SR, SCI-SHY-SR, SCI-OBS-SR, SCI-ABS-SR). This was a cross-sectional study involving a clinical sample of adult obese patients with severe obesity (average body mass index = 45 ± 8 kg m(-2) ) and candidate to bariatric surgery who were recruited between November 2001 and November 2010 at the Obesity Center of the Endocrinology Unit, University Hospital of Pisa. All participants completed a face-to-face interview, including a diagnostic assessment of axes-I and II mental disorders (using the Structured Clinical Interview for Manual of Mental Disorders, fourth edition [SCID]-I and SCID-II) and filled out self-report spectrum instruments. Among obese patients not affected by BE, eating dyscontrol was highly represented. Indeed, 39.7% (N = 177) of subjects endorsed six or more items of the Anorexia-Bulimia Spectrum Self-Report, lifetime version domain exploring this behaviour. The cumulative probability of having axis-I, axis-II and a spectrum condition disorder increased significantly with the number of eating dyscontrol items endorsed. In both BE and NBE obese subjects, eating dyscontrol may represent an independent dimension strongly related to the spectrum psychopathology and axes I/II disorders. A systematic screening for eating dyscontrol symptoms by means of self-report spectrum instruments may be valuable to assign specific treatment strategies.


Assuntos
Transtornos de Ansiedade/psicologia , Cirurgia Bariátrica , Transtorno da Compulsão Alimentar/psicologia , Obesidade Mórbida/psicologia , Adulto , Transtornos de Ansiedade/diagnóstico , Transtorno da Compulsão Alimentar/diagnóstico , Índice de Massa Corporal , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/prevenção & controle , Obesidade Mórbida/cirurgia , Seleção de Pacientes , Inventário de Personalidade , Medição de Risco
14.
J Endocrinol Invest ; 38(2): 125-31, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25501840

RESUMO

BACKGROUND: While it is now accepted that genes and their products affect food intake, the concept that locomotor behavior or the propensity for physical activity is controlled by neuro hum oral regulators is frequently underappreciated. In mammals, complex interactions have developed to allow the cross-talk between fuel homeostasis and physical activity. AIM: The aim of this review is to provide a synopsis of the influence of the leptin-melanocortin pathway, a well-studied pivotal player in body weight regulation, on locomotor behaviors. CONCLUSIONS: In rodents, reductions in leptin levels that physiologically occur following acute food deprivation or a reduction of the fat mass consequent to prolonged caloric restrictions are associated with a decrease in total locomotor activity and simultaneous increase in food-anticipatory activity, a locomotor behavior which reflects a foraging attitude. These actions can be prevented by leptin administration and are at least partially mediated by the neurons of the melanocortin pathway. In humans, twin studies have attributed to genetic factors approximately 50% of the variance of physical activity. An elevated number of the genes or loci which may affect physical activity are involved in body weight homeostasis. Polymorphisms of the melanocortin-4 and leptin receptors have repeatedly been associated with the level of physical activity. Unraveling the complexity of the regulation of locomotor behavior and the interconnections with the pathways involved in energy homeostasis may help explain the substantial individual variability in physical activities in humans and disentangle the harmful effects of sedentary lifestyle, which may be distinct from the detrimental effects of obesity.


Assuntos
Homeostase/fisiologia , Leptina/fisiologia , Melanocortinas/fisiologia , Atividade Motora/fisiologia , Transdução de Sinais/fisiologia , Animais , Humanos
15.
AJNR Am J Neuroradiol ; 36(3): 562-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25395658

RESUMO

BACKGROUND AND PURPOSE: Physiologic and pathologic arterial tortuosity may attenuate blood flow pulsatility. The aim of this prospective study was to assess a potential effect of the curved V3 segment (Atlas slope) of the vertebral artery on arterial flow pulsatility. The pulsatility index and resistance index were used to assess blood flow pulsatility. MATERIALS AND METHODS: Twenty-one healthy volunteers (17 men, 4 women; mean age, 32 years) were examined with a 3T MR imaging system. Blood velocities were measured at 2 locations below (I and II) and at 1 location above the V3 segment (III) of the vertebral artery by using a high-resolution 2D-phase-contrast sequence with multidirectional velocity-encoding. RESULTS: Pulsatility and resistance indices decreased along all measurement locations from proximal to distal. The pulsatility index decreased significantly from location II to III and from I to II. However, the decrease was more pronounced along the Atlas slope than in the straight-vessel section below. The decrease of the resistance index was highly significant along the Atlas slope (location II to III). The decrease from location I to II was small and not significant. CONCLUSIONS: The pronounced decrease in pulsatility and resistance indices along the interindividually uniformly bent V3 segment compared with a straight segment of the vertebral artery indicates a physiologic attenuating effect of the Atlas slope on arterial flow pulsatility. A similar effect has been described for the carotid siphon. A physiologic reduction of pulsatility in brain-supplying arteries would be in accordance with several recent publications reporting a correlation of increased arterial flow pulsatility with leukoencephalopathy and lacunar stroke.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Angiografia por Ressonância Magnética , Fluxo Pulsátil/fisiologia , Artéria Vertebral/fisiologia , Adulto , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Estudos Prospectivos , Resistência Vascular , Adulto Jovem
16.
Minerva Med ; 105(6): 487-95, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25274462

RESUMO

The prevalence of aortic valve stenosis (AS) is growing in developed countries because its prevalence increases with age. A growing number of elderly patients are currently referred to specialized centres to be evaluated for potential therapeutic strategies. Indeed, two techniques are nowadays able to treat high-risk AS patients: TAVI and surgical replacement (AVR). It is the purpose of the present review to summarize current knowledge on safety and efficacy of AVR and TAVI in high-risk patients; to focus on some aspects of recently published guidelines; to emphasize the growing importance of pre-operative individual risk assessment, which is considered the real crucial point for patient selection and trial's comparisons. Indeed, it is worth of noting that currently adopted risk-scores do not show satisfactory performances. Accordingly, it becomes of utmost importance to investigate several baseline but still neglected patients' characteristics (e.g. frailty, functional status, co-morbid conditions, etc.), as well as their pathogenetic relationships with interventional results and follow-up prognosis. All these items are emphasized in the present review. Finally, we have tried to anticipate future scenarios in terms of both ongoing clinical trials and improvements of risk-scores.


Assuntos
Estenose da Valva Aórtica/cirurgia , Medição de Risco , Substituição da Valva Aórtica Transcateter , Idoso , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/epidemiologia , Ensaios Clínicos como Assunto , Comorbidade , Seguimentos , Idoso Fragilizado , Implante de Prótese de Valva Cardíaca , Humanos , Ataque Isquêmico Transitório/epidemiologia , Estudos Multicêntricos como Assunto , Readmissão do Paciente/estatística & dados numéricos , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Guias de Prática Clínica como Assunto , Prevalência , Prognóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/epidemiologia , Análise de Sobrevida , Avaliação de Sintomas , Resultado do Tratamento
17.
Ann Ig ; 26(3): 195-204, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24998210

RESUMO

AIM: Aim of this study was to validate the Comprehensive Appropriateness Scale for the Care of Obesity in Rehabilitation (CASCO-R) and to determine the cut-off score for indicating the most appropriate health care setting for patients with obesity. METHODS: The CASCO-R scale was developed according to the available scientific literature and expertise of an expert panel working for a Consensus document endorsed by the Italian Society of Obesity (SIO) and the Italian Society for the Study of Eating Disorders (SISDCA). 16 Italian centres, specialized in the treatment of obesity, characterised by different settings of care (specialist outpatient service, day-hospital service, intensive inpatient rehabilitation), participated in the study. RESULTS: 449 obese subjects were enrolled in the study (30.5% males and 69.5% females): 38.3% from outpatient services, 20.7% from day-hospital services and 40.9% from intensive inpatient rehabilitation units. After 2-month of treatment, a workload summary sheet, including medical and nursing interventions, number of expert advices and diagnostic procedures, and adverse clinical events (ACEs) was fulfilled for each patient. Statistically significant correlation was found between the CASCO-R scale score, overall workload and ACEs. The CASCO-R scale demonstrated also an excellent performance in terms of internal validity and test-retest analysis. Three total score cut-off have been proposed: >25 for inpatient intensive rehabilitation; 20-25 for day-hospital service; <20 for outpatient treatment. CONCLUSIONS: In conclusion, the CASCO-R scale was demonstrated to be a valid tool for assessing the appropriateness of the choice of the level of care. Hence, it can be used to verify the proper allocation of patients, as it was well correlated with measures of workload and the incidence of ACEs.


Assuntos
Assistência à Saúde/normas , Obesidade Mórbida/terapia , Qualidade da Assistência à Saúde , Adulto , Idoso , Assistência Ambulatorial/organização & administração , Assistência Ambulatorial/normas , Assistência à Saúde/organização & administração , Feminino , Hospitalização , Humanos , Incidência , Itália , Masculino , Pessoa de Meia-Idade , Carga de Trabalho/estatística & dados numéricos
18.
J Evol Biol ; 27(8): 1536-48, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24890604

RESUMO

Sharks occupy marine habitats ranging from shallow, inshore environments to pelagic, and deepwaters, and thus provide a model system for testing how gross habitat differences have shaped vertebrate macroevolution. Palaeontological studies have shown that onshore lineages diversify more quickly than offshore taxa. Among onshore habitats, coral reef-association has been shown to increase speciation rates in several groups of fishes and invertebrates. In this study, we investigated whether speciation rates are habitat dependent by generating the first comprehensive molecular timescale for shark divergence. Using phylogenetic comparative methods, we rejected the hypothesis that shelf (i.e. onshore) lineages have higher speciation rates compared to those occupying deepwater and oceanic (i.e. offshore) habitats. Our results, however, support the hypothesis of increased speciation rates in coral reef-associated lineages within the Carcharhinidae. Our new timetree suggests that the two major shark lineages leading to the extant shark diversity began diversifying mostly after the end-Permian mass extinction: the squalimorphs into deepwater and the galeomorphs into shelf habitats. We suggest that the breakdown of the onshore-offshore speciation rate pattern in sharks is mediated by success in deepwater environments through ecological partitioning, and in some cases, the evolution of morphological novelty.


Assuntos
Evolução Biológica , Ecossistema , Especiação Genética , Filogenia , Tubarões/fisiologia , Animais , Simulação por Computador , Recifes de Corais , Geografia , Modelos Genéticos , Tubarões/genética
19.
Int J Cardiovasc Imaging ; 30(2): 323-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24221905

RESUMO

To test feasibility of myocardial T1 mapping of the right ventricle (RV) at systole when myocardium is more compact and to determine the most appropriate imaging plane. 20 healthy volunteers (11 men; 33 ± 8 years) were imaged on a 1.5T scanner (MAGNETOM Avanto, Siemens AG, Erlangen, Germany). A modified look-locker inversion-recovery sequence was acquired at mid-ventricular short axis (SAX), as horizontal long-axis view and as transversal view at systole (mean trigger time 363 ± 37 ms). Myocardial T1 time of the left-ventricular and RV myocardium was measured within a region of interest (ROI) on generated T1-maps. The most appropriate imaging plane for the RV was determined by the ability to draw a ROI including the largest amount of myocardium without including adjacent tissue or blood. At systole, when myocardium is thicker, measurements of the RV myocardium were feasible in 18/20 subjects. Average size of the ROI was 0.42 ± 0.28 cm(2). In 10/18 subjects, short axis was the most appropriate imaging plane to obtain measurements (p = 0.034). Average T1 time of the RV myocardium was 1,016 ± 61 ms, and average T1 of the left-ventricular (LV) was 956 ± 25 ms (p < 0.001). T1 mapping of the RV myocardium is feasible during systole in the majority of healthy subjects but with a small ROI only. SAX plane was the optimal imaging plane in the majority of subjects. Native myocardial T1 time of the RV is significantly longer compared to the LV, which might be explained by the naturally higher collagen content of the RV.


Assuntos
Ventrículos do Coração/anatomia & histologia , Imagem Cinética por Ressonância Magnética , Miocárdio , Adulto , Colágeno/análise , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Ventrículos do Coração/química , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/química , Valor Preditivo dos Testes , Valores de Referência , Sístole , Função Ventricular Direita , Adulto Jovem
20.
Clin Ter ; 164(5): e437-44, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24217846

RESUMO

Hepatitis C virus infection and diabetes mellitus are two worldwide, major public health problems with increasing complication and mortality rates. Type 1 diabetes mellitus (T1D) is characterized by an autoimmune process leading to pancreatic beta cell destruction; only when the major part of pancreatic beta cells have been destroyed the diabetes become clinically manifest. At the basis of the development of the T1D there is an interplay among environmental factors, pancreatic beta cells, the innate and adaptive immune system, the genetic background and the comorbidities of the patient. Viral infections, including hepatitis C virus infection, may be one of the factors that can almost accelerate progression to diabetes, through different mechanisms.


Assuntos
Doenças Autoimunes/etiologia , Diabetes Mellitus Tipo 1/etiologia , Hepacivirus/patogenicidade , Hepatite C Crônica/complicações , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Doenças Autoimunes/imunologia , Autoimunidade/efeitos dos fármacos , Comorbidade , Citocinas/metabolismo , Efeito Citopatogênico Viral , Diabetes Mellitus Tipo 1/imunologia , Suscetibilidade a Doenças , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Resistência à Insulina , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/virologia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/imunologia , Tireoidite Autoimune/etiologia , Tireoidite Autoimune/imunologia
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